The occurrence of acute leukemia after treatment of a primary malignancy is a problem of increasing concern to clinical oncologists. It is not clear if these patients are particularly cancer-prone, or if the treatment regime, radiation chemotherapy, or a combination of the two, induces the leukemic transformation. I have just completed the chromosome analysis with banding of leukemic cells from ten patients with acute nonlymphocytic leukemia following treated malignant lymphoma. Each of these patients had a chromosomally abnormal clone of cells; in 9 patients one B chromosome was missing which was identified as a No. 5 in 8. In our ten patients, the median time for the onset of leukemia was 58 months following the diagnosis of malignant lymphoma. Six of 9 patients had a preleukemic phase 2-20 months prior to overt leukemia. I plan to study the role of the previous malignancy and the type of previous therapy by investigating bone marrow chromosomes in the following four groups of patients: (1) patients treated for malignant lymphoma, (2) breast cancer patients given preventative chemotherapy post operatively, (3) patients with gynecological malignancies, particularly ovarian cancer, treated with an alkylating agent and (4) post-renal transplant patients. A bone marrow aspiration will be obtained from each patient initially and approximately every two years thereafter. An abnormal karyotype in a patient who previously was normal would confirm the diagnosis of a preleukemic phase. This investigation will establish whether nonrandom chromosome changes can be detected prior to the development of leukemia, whether the frequency and type of abnormality is different in the various clinical groups, or can be related to the type of treatment regimen. This study will contribute to our understanding of the role of chromosome abnormalities in leukemogenesis, and permit the earlier detection of patients at risk.